Transcatheter Aortic-Valve Replacement with a Balloon-Expandable Valve in Low-Risk Patients.

Background: Among patients with aortic stenosis who are at intermediate or high risk for death with surgery, major outcomes are similar with transcatheter aortic-valve replacement (TAVR) and surgical aortic-valve replacement. There is insufficient evidence regarding the comparison of the two procedures in patients who are at low risk.

Methods: We randomly assigned patients with severe aortic stenosis and low surgical risk to undergo either TAVR with transfemoral placement of a balloon-expandable valve or surgery.

Examination of the role of sphingosine kinase 2 in a murine model of systemic lupus erythematosus.

Systemic lupus erythematosus is an autoimmune disease characterized by overproduction of type 1 IFN that causes multiple organ dysfunctions. Plasmacytoid dendritic cells (pDCs) that secrete large amounts of IFN have recently been implicated in the initiation of the disease in preclinical mouse models. Sphingosine-1-phosphate, a bioactive sphingolipid metabolite, is produced by 2 highly conserved isoenzymes, sphingosine kinase (SphK) 1 and SphK2, and regulates diverse processes important for immune responses and autoimmunity.

Neuroimaging-Based Classification Algorithm for Predicting 1p/19q-Codeletion Status in -Mutant Lower Grade Gliomas.

Background And Purpose: ()-mutant lower grade gliomas are classified as oligodendrogliomas or diffuse astrocytomas based on 1p/19q-codeletion status. We aimed to test and validate neuroradiologists' performances in predicting the codeletion status of -mutant lower grade gliomas based on simple neuroimaging metrics.

Materials And Methods: One hundred two -mutant lower grade gliomas with preoperative MR imaging and known 1p/19q status from The Cancer Genome Atlas composed a training dataset.

Directed evolution of super-secreted variants from phage-displayed human Interleukin-2.

Selection from a phage display library derived from human Interleukin-2 (IL-2) yielded mutated variants with greatly enhanced display levels of the functional cytokine on filamentous phages. Introduction of a single amino acid replacement selected that way (K35E) increased the secretion levels of IL-2-containing fusion proteins from human transfected host cells up to 20-fold. Super-secreted (K35E) IL-2/Fc is biologically active in vitro and in vivo, has anti-tumor activity and exhibits a remarkable reduction in its aggregation propensity- the major manufacturability issue limiting IL-2 usefulness up to now.

Anesthesiologist Specialization and Use of General Anesthesia for Cesarean Delivery.

Background: Guidelines for obstetric anesthesia recommend neuraxial anesthesia (i.e., spinal or epidural block) for cesarean delivery in most patients.

Accuracy of Fractional Flow Reserve Derived From Coronary Angiography.

Background: Measuring fractional flow reserve (FFR) with a pressure wire remains underutilized because of the invasiveness of guide wire placement or the need for a hyperemic stimulus. FFR derived from routine coronary angiography (FFR) eliminates both of these requirements and displays FFR values of the entire coronary tree. The FFR Accuracy versus Standard FFR (FAST-FFR) study is a prospective, multicenter, international trial with the primary goal of determining the accuracy of FFR.

A review of racial/ethnic disparities in pediatric trauma care, treatment, and outcomes.

Health disparities are an increasingly researched topic in the United States. Evidence of disparities found across the spectrum of health care includes pediatric patients. The purpose of this review is to comprehensively summarize disparities among pediatric trauma patients, evaluating both emergency department and hospital treatment and outcomes.

A cluster randomised controlled trial of two rounds of mass drug administration in Zanzibar, a malaria pre-elimination setting-high coverage and safety, but no significant impact on transmission.

Background: Mass drug administration (MDA) has the potential to interrupt malaria transmission and has been suggested as a tool for malaria elimination in low-endemic settings. This study aimed to determine the effectiveness and safety of two rounds of MDA in Zanzibar, a pre-elimination setting.

Methods: A cluster randomised controlled trial was conducted in 16 areas considered as malaria hotspots, with an annual parasite index of > 0.

A non-canonical SWI/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation.

Mammalian SWI/SNF chromatin remodelling complexes exist in three distinct, final-form assemblies: canonical BAF (cBAF), PBAF and a newly characterized non-canonical complex (ncBAF). However, their complex-specific targeting on chromatin, functions and roles in disease remain largely undefined. Here, we comprehensively mapped complex assemblies on chromatin and found that ncBAF complexes uniquely localize to CTCF sites and promoters.

Prediction of Ambulatory Hypertension Based on Clinic Blood Pressure Percentile in Adolescents.

Ambulatory blood pressure (BP) monitoring provides a more precise measure of BP status than clinic BP and is currently recommended in the evaluation of high BP in children and adolescents. However, ambulatory BP monitoring may not always be available. Our aim was to determine the clinic BP percentile most likely to predict ambulatory hypertension.

Outcomes Among Patients Undergoing Distal Left Main Percutaneous Coronary Intervention.

Background: Distal left main (LM) coronary artery bifurcation disease increases percutaneous coronary intervention (PCI) procedural complexity and is associated with worse outcomes than isolated ostial/shaft disease. The optimal treatment strategy for distal LM disease is undetermined. We sought to determine whether outcomes after PCI of LM distal bifurcation lesions are influenced by treatment with a provisional 1-stent versus planned 2-stent technique, and if so, whether such differences are conditioned by the complexity of the LM bifurcation lesion.

Endothelial Cell-Specific Inactivation of TSPAN12 (Tetraspanin 12) Reveals Pathological Consequences of Barrier Defects in an Otherwise Intact Vasculature.

Objective- Blood-CNS (central nervous system) barrier defects are implicated in retinopathies, neurodegenerative diseases, stroke, and epilepsy, yet, the pathological mechanisms downstream of barrier defects remain incompletely understood. Blood-retina barrier (BRB) formation and retinal angiogenesis require β-catenin signaling induced by the ligand norrin (NDP [Norrie disease protein]), the receptor FZD4 (frizzled 4), coreceptor LRP5 (low-density lipoprotein receptor-like protein 5), and the tetraspanin TSPAN12 (tetraspanin 12). Impaired NDP/FZD4 signaling causes familial exudative vitreoretinopathy, which may lead to blindness.

Onset of analgesia by a topically administered flurbiprofen lozenge: a randomised controlled trial using the double stopwatch method.

Background: The double stopwatch (DSW) method for determining the onset of analgesic activity has been implemented extensively by investigators studying orally administered drugs.

Objective: The aim of this randomised, placebo-controlled trial was to use the DSW method to determine the time to onset of analgesia of a single dose of a topically administered non-steroidal anti-inflammatory drug, flurbiprofen 8.75 mg lozenge.

Towards an Evidence-Based Recommendation for a Balanced Breakfast-A Proposal from the International Breakfast Research Initiative.

The International Breakfast Research Initiative (IBRI) set out to derive nutritional recommendations for a balanced breakfast using a standardized analysis of national nutrition surveys from Canada, Denmark, France, Spain, UK and the US. In all countries, the frequency of breakfast consumption by age was high and U-shaped with children and older adults having a higher frequency of breakfast consumption. Breakfast contributed 16% to 21% of daily energy intake.

Olfactory receptor OR2AT4 regulates human hair growth.

Olfactory receptors are expressed by different cell types throughout the body and regulate physiological cell functions beyond olfaction. In particular, the olfactory receptor OR2AT4 has been shown to stimulate keratinocyte proliferation in the skin. Here, we show that the epithelium of human hair follicles, particularly the outer root sheath, expresses OR2AT4, and that specific stimulation of OR2AT4 by a synthetic sandalwood odorant (Sandalore) prolongs human hair growth ex vivo by decreasing apoptosis and increasing production of the anagen-prolonging growth factor IGF-1.

Cardiovascular and Noncardiovascular Death After Percutaneous Coronary Intervention: Insights From 32 882 Patients Enrolled in 21 Randomized Trials.

Background: Despite advances in technology and technique, a substantial proportion of patients still die within several years after percutaneous coronary intervention (PCI). The relative rates of cardiovascular and noncardiovascular death after PCI remain uncertain.

Methods And Results: We pooled individual patient-level data from 21 randomized clinical trials of PCI performed in 32 882 patients.

Angiogenesis PET Tracer Uptake (Ga-NODAGA-E[(cRGDyK)]₂) in Induced Myocardial Infarction and Stromal Cell Treatment in Minipigs.

Angiogenesis is considered integral to the reparative process after ischemic injury. The αβ₃ integrin is a critical modulator of angiogenesis and highly expressed in activated endothelial cells. Ga-NODAGA-E[(cRGDyK)]₂ (RGD) is a positron-emission-tomography (PET) ligand targeted towards αβ₃ integrin.

Class I HDAC inhibition is a novel pathway for regulating astrocytic apoE secretion.

Despite the important role of apolipoprotein E (apoE) secretion from astrocytes in brain lipid metabolism and the strong association of apoE4, one of the human apoE isoforms, with sporadic and late onset forms of Alzheimer's disease (AD) little is known about the regulation of astrocytic apoE. Utilizing annotated chemical libraries and a phenotypic screening strategy that measured apoE secretion from a human astrocytoma cell line, inhibition of pan class I histone deacetylases (HDACs) was identified as a mechanism to increase apoE secretion. Knocking down select HDAC family members alone or in combination revealed that inhibition of the class I HDAC family was responsible for enhancing apoE secretion.

Human protective response induced by meningococcus B vaccine is mediated by the synergy of multiple bactericidal epitopes.

4CMenB is the first broad coverage vaccine for the prevention of invasive meningococcal disease caused by serogroup B strains. To gain a comprehensive picture of the antibody response induced upon 4CMenB vaccination and to obtain relevant translational information directly from human studies, we have isolated a panel of human monoclonal antibodies from adult vaccinees. Based on the Ig-gene sequence of the variable region, 37 antigen-specific monoclonal antibodies were identified and produced as recombinant Fab fragments, and a subset also produced as full length recombinant IgG1 and functionally characterized.

Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder: Synopsis of the Kidney Disease: Improving Global Outcomes 2017 Clinical Practice Guideline Update.

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a selective update of the prior CKD-MBD guideline published in 2009. The guideline update and the original publication are intended to assist practitioners caring for adults with CKD and those receiving long-term dialysis.

Methods: Development of the guideline update followed an explicit process of evidence review and appraisal.

Standardized Definition of Structural Valve Degeneration for Surgical and Transcatheter Bioprosthetic Aortic Valves.

Bioprostheses are prone to structural valve degeneration, resulting in limited long-term durability. A significant challenge when comparing the durability of different types of bioprostheses is the lack of a standardized terminology for the definition of a degenerated valve. This issue becomes especially important when we try to compare the degeneration rate of surgically inserted and transcatheter bioprosthetic valves.

Increased Mortality Rates With Prolonged Corticosteroid Therapy When Compared With Antitumor Necrosis Factor-α-Directed Therapy for Inflammatory Bowel Disease.

Objectives: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that compromise quality of life and may increase mortality. This study compared the mortality risk with prolonged corticosteroid use vs. antitumor necrosis factor-α (anti-TNF) drugs in IBD.

Human Papillomavirus (HPV)-associated Lymphoepithelioma-like Carcinoma of the Vagina and Anal Canal: A Rare Variant of Squamous Cell Carcinoma.

Lymphoepithelioma-like carcinoma (LELC) is an uncommon variant of squamous cell carcinoma, which is histologically identical to lymphoepithelial carcinoma of the nasopharynx. LELCs have been reported at a variety of sites, including the stomach, salivary gland, thymus, cervix, endometrium, breast, skin, bladder, and lung. We report 2 LELCs of the vagina and 1 of the anal canal, the first report of LELC at the latter site.